Body’s response to injury and inflammation may hinder wound healing in diabetes

‘NETs’ slow healing in diabetic mice, may contribute to delayed healing in people with diabetes

Boston Children’s Hospital

One of the body’s own tools for preventing wound infections may actually interfere with wound healing, according to new research from Boston Children’s Hospital. In a study published online in Nature Medicine, scientists from the hospital’s Program in Cellular and Molecular Medicine (PCMM) found they could speed up wound healing in diabetic mice by keeping immune cells called neutrophils from producing bacteria-trapping neutrophil extracellular traps (NETs).

The study, led by PCMM senior investigator Denisa Wagner, Ph.D., and postdoctoral fellow Siu Ling Wong, Ph.D., suggests that methods of preventing NET production or of cleaving NETs in a wound could, one day, possibly help alleviate wound healing problems in patients with diabetes.

Halo MINI negative pressure wound therapy pump system is now being used for hard to heal wounds. The NPWT pump helps extract exudate from the wound and promote oxidation in the wound.

Delayed wound healing is a common complication of both Type 1 and Type 2 diabetes. Open diabetic foot ulcers, for example, affect a quarter of people with diabetes and are a leading cause of amputations.

When the skin is cut or broken, the body mobilizes a complicated array of cells and proteins to stop bleeding, prevent infection by triggering inflammation and start the healing process. As part of the inflammatory response, neutrophils, which ingest and destroy bacteria, expel their own chromatin (a mix of DNA and associated proteins) in the form of NETs within the wound.

While possibly beneficial as a tool for keeping bacteria out of the body, NETs also have a dark side. ‘NETs predispose patients to inflammation, heart disease and deep vein thrombosis [dangerous blood clots that form within veins deep inside the body], all of which are elevated in patients with diabetes,’ says Wagner, who is also the Edwin Cohn Professor of Pediatrics at Harvard Medical School.

To see whether diabetes primes neutrophils to produce NETs, Wagner, Wong and colleagues at Joslin Diabetes Center and Pennsylvania State University examined neutrophils from patients with either Type 1 or Type 2 diabetes, finding that the cells contained four times the normal amount of PAD4 (a key enzyme in the NET production process) and made more NETs when stimulated. Further lab experiments revealed that neutrophils from healthy donors or mice when exposed to excessive glucose — mimicking the diabetic environment — were also more likely to release NETs than those incubated in normal glucose levels.

Diabetic mice in the study had more NETs in wounds and healed more slowly than normal mice. However, Wagner and Wong’s team found that healing was accelerated in diabetic mice that lacked PAD4 (and therefore could not produce NETs).

To see whether cleaving NETs would have an effect similar to preventing their production, the research team treated mice with DNase 1 (an enzyme that breaks up DNA and therefore can destroy NETs). After three days, wounds on DNase 1-treated diabetic animals were 20 percent smaller than on untreated animals. Interestingly, DNase 1-treatment appeared to accelerate wound healing in healthy mice as well.

Wagner and Wong explain that NETs may impede wound healing in part because the dense, toxic mesh they produce interferes with new skin cells trying to enter the wound site. They also suggest that NETs may be redundant as a defense mechanism against bacteria.

‘We don’t fully understand the functions of NETs, but all of the other antimicrobial functions of neutrophils are preserved even if they cannot make NETs,’ Wagner notes. ‘Any injury that causes inflammation will result in production of NETs, and we think that if the injury involves skin repair, NETs will hinder the repair process.’


The study was supported by the American Diabetes Association (Innovation Award 7-13-IN-44); the National Heart, Lung and Blood Institute (grant number R01HL102101); the National Cancer Institute (grant number R01HL136856); the National Institute of Diabetes and Digestive and Kidney Diseases (grant number R01DK031036) and a GlaxoSmithKline/Immune Disease Institute Alliance Fellowship.

Flesh eating bacteria in Florida water

It’s a rare bacteria thriving in Florida’s warm sea waters, sparking a string of illnesses and even two deaths in the sunny southern state. Health officials are warning beachgoers about Vibrio vulnificus, but they’re also trying to dispel rumours that the nasty bacteria is “flesh-eating.”

The bacteria has infected eight people and killed two more this year in Florida, according to U.S. reports. It’s found in warm marine waters – if people swim with open wounds, or eat contaminated seafood, they could come in contact with the germs.

“People get vibrio by swimming, wading and playing in salt or brackish waters with open wounds or scratches or by eating undercooked or raw shellfish, particularly oysters. Vibrio is rare but can be a serious disease,” Dr. Carina Blackmore, Florida’s Deputy State Epidemiologist, said in a video put together by the health department.

Halo MINI Negative Pressure Wound Therapy pump system and universal black foam wound dressing wound help heal complicated wounds.

“The best way of protecting yourself from infections from vibrio is by performing good wound care, and you do that by covering the wounds with dry, clean bandages until they’re healed and pay attention to minor wounds, scratches and blisters…,” she said.

While it’s incredibly rare – last year, there were about 32 cases in Florida – the infection can lead to vomiting, diarrhea, and stomach pain similar to symptoms of a stomach flu.

READ MORE: Suspected use of flesh-eating drug, Krokodil, unconfirmed, police say

Handfuls of U.S. reports suggest that when the bacterium infects an open wound, it can lead to skin ulcers, akin to “flesh eating.” The bacteria doesn’t eat the flesh, but it can lead to infection. In some cases, amputation is required if infection is severe enough.

Last August, health officials had their hands full in making clarifications about the bacteria. Ultimately, Florida’s Department of Health for Pinellas County issued its own “Myth Buster” report.

“The naturally occurring organisms in the vibrio family have been in the news this week, but a lot of ‘myth information’ has scared beachgoers and visitors,” Maggie Hall, the department’s spokesman said, according to one outlet.

Hall said it’s not flesh-eating, contrary to reports. “There is no such medical term and the organism is not a Pac-man consuming pac-dots,” she said.

On Friday, the department put together another press release to correct “inaccuracies about Florida’s beach water.” It suggests its warning is a routine measure as vibrio infections typically pick up between May and October.

CPH offers Breast Health navigators

Central Peninsula Hospital (CPH) starting late exhibited another framework for gathering people stood up to with the mind-boggling test of a chest tumor finding. Nearby the obvious anxiety and wellbeing stresses that run as an inseparable unit with such a discovering, the starting measure of information, tests and decisions to be made can be additionally over-whelming for the patient. While having the support of friends and family is precious, CPH starting late obtained two new Breast Health Navigators, neighborhood RN’s who got excellent planning in Atlanta, GA and returned home to give what the title recommends: help patients investigate their approach to recovery. “What I fulfill for patients who have been resolved to have chest illness is serve as a specialist or pilot for them. I help guide them through the plan of medicines and the chemotherapy, the therapeutic checkups, the inherited qualities advocate and the nutritionist. I’m a relentless enrollment point for all of them through their experiences,” cleared up Heather Moon, RN at CPH and a starting late arranged patient pilot.

Equinox Medical, LLC. is the manufactures the latest universal negative pressure wound therapy black foam wound dressing and white foam dressing in the United States.

“For a few patients, especially most importantly, having a pilot can have all the impact in the effortlessness with which they progress through the uncharted space of their definite trip: the early on examination, the treatment and finally survivorship. In conjunction with arranging treatment, controls also help direct patients towards distinctive resources in our gathering, for instance, chest prosthesis and wigs. After surgery we help with postliminary: wound care and dressing changes, whatever a patient who is encountering chest malady may need,” said Moon. “What I encourage patients to do is to just manage themselves and we will help manage their thought and likewise help them fathom what is striking them and what’s in store next,” she said in conveying the longing of CPH to get the word out to the gathering. “Despite the way that the Breast Cancer framework has been a bit of CPH for quite a while, in beginning the new program CPH is endeavoring to pass on more thoughtfulness regarding the gathering. We have to tell the gathering that we’re here for them, they don’t have to go to Anchorage any more to get the thought they need,” said Moon. Quickly with the expertise of Heather and Amber Avery as patient pilots, close by the straggling leftovers of the qualified staff at CPH, patients and their families resolved to have chest tumor have section to glorious care and bearing right here at home.